Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.

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Title: Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.
Authors: Flores BN; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; insitro, South San Francisco, CA, 94080, USA., Yu SB; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Cohen IV; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Fanok MH; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Luan W; Neurodegeneration Pathobiology Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia., Maciuca RD; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Sun LD; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Regeneron Pharmaceuticals Inc., Tarrytown, NY, 10591, USA., Tsai RM; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Vissers M; Centre for Human Drug Research; Zernikedreef 8, 2333 CL, Leiden, the Netherlands., Smits L; Centre for Human Drug Research; Zernikedreef 8, 2333 CL, Leiden, the Netherlands.; Leiden University Medical Center; Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., Bunte TM; The University Medical Center Utrecht; Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands., Bakardjiev A; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Gilead Sciences Inc., Foster City, CA, 94404, USA., Balasundar S; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Calvert MEK; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Chin MY; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Dobbins SK; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Dowdle WE; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Altos Labs, Redwood City, CA, 94065, USA., Fang M; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Heuberger JAAC; Centre for Human Drug Research; Zernikedreef 8, 2333 CL, Leiden, the Netherlands., Ha CL; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Huang F; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Takeda Pharmaceuticals America, Inc., Boston, MA, 02215, USA., Miyamoto T; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Osipov M; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Septerna, South San Francisco, CA, 94080, USA., Madrid San Martin L; Neurodegeneration Pathobiology Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia., Saund K; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Tatarakis D; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Vu AQ; Dept of Cellular and Molecular Medicine, University of California; San Diego, La Jolla, CA, 92037, USA., Xiong C; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Gilead Sciences Inc., Foster City, CA, 94404, USA., Yeo GW; Dept of Cellular and Molecular Medicine, University of California; San Diego, La Jolla, CA, 92037, USA.; Sanford Stem Cell Institute and Stem Cell Program, UC San Diego, La Jolla, CA, 92037, USA.; Institute for Genomic Medicine, UC San Diego, La Jolla, CA, 92037, USA.; Sanford Laboratories for Innovative Medicines, La Jolla, CA, 92037, USA., Groeneveld GJ; Centre for Human Drug Research; Zernikedreef 8, 2333 CL, Leiden, the Netherlands.; Leiden University Medical Center; Albinusdreef 2, 2333 ZA, Leiden, the Netherlands., van den Berg LH; The University Medical Center Utrecht; Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands., Dhuria S; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Estrada AA; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Tenvie Therapeutics Inc., South San Francisco, CA, 94080, USA., Jennings D; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Sandmann T; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Ho C; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA., Scearce-Levie K; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Takeda Pharmaceuticals America, Inc., Boston, MA, 02215, USA., Yulyaningsih E; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA.; Tenvie Therapeutics Inc., South San Francisco, CA, 94080, USA., Walker AK; Neurodegeneration Pathobiology Laboratory, Clem Jones Centre for Ageing Dementia Research, Queensland Brain Institute, The University of Queensland, St Lucia, QLD, 4072, Australia.; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia., Di Paolo G; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA. dipaolo@dnli.com., Kane LA; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA. lesleykane@gmail.com., Troyer MD; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA. troyer@dnli.com., Lewcock JW; Denali Therapeutics Inc.; 161 Oyster Point Blvd., South San Francisco, CA, 94080, USA. lewcock@dnli.com.
Source: Nature communications [Nat Commun] 2025 Aug 18; Vol. 16 (1), pp. 7690. Date of Electronic Publication: 2025 Aug 18.
Publication Type: Journal Article; Randomized Controlled Trial; Clinical Trial, Phase I
Journal Info: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Database: MEDLINE Ultimate
Description
ISSN:2041-1723
DOI:10.1038/s41467-025-63031-y